Invasive Lobular Carcinoma Has Higher Immune Response Than Invasive Ductal Carcinoma in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancers
Bibliographic record
Abstract
Background: Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are two major pathological diagnoses of breast cancer, but few studies have described their differences within luminal (estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative) subtypes at the molecular level. Methods: Using The Cancer Genome Atlas (TCGA) (n = 584) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1,355) cohorts, we analyzed luminal ILC and IDC, excluding mixed type, in patients with stage I-III breast cancer. Results: ILC was associated with Nottingham histological grade 2, larger tumor size and more stage III disease than IDC (all P < 0.01) but no difference in lymph node nor distant metastasis in both cohorts. There was no survival difference between ILC and IDC. ILC had less aggressive genomic features compared to IDC, and the cell proliferation score and Ki67 gene expression were significantly lower in ILC in TCGA (P < 0.001); however, these findings were not validated in METABRIC. Hallmark cell proliferation-related gene sets (E2F targets, G2M checkpoint, MYC targets V1, and MTORC1 signaling) were significantly less enriched in ILC in both cohorts (all normalized enrichment score (NES) > 1.4, false discovery rate (FDR) < 0.12). While ILC appeared to have a lower trend of pathological complete response (pCR) in the GSE20194 and GSE1140494 cohorts, ILC was infiltrated with significantly more CD4+ cells and dendritic cells and significantly less T helper type I (Th1) cells, regulatory T cells and M1 and M2 macrophages in both cohorts (all P < 0.05). Stromal cells, adipocytes and lymphatic endothelial cells were highly infiltrated in ILC, and cytolytic activity that represented the global anti-tumor immunity was significantly elevated in ILC in TCGA and subsequently validated in METABRIC. Conclusions: ILC has higher immune response and immune cell infiltration than IDC in the luminal subtype.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".